1. Field of the Invention
The invention relates to a method for treatment of malaria using a flavonoid glycoside compound.
2. Description of the Related Art
As the most frequent parasitosis on the earth, malaria is a potential deadly disease transmitted through anopheles. According to the World Health Organization (WHO), there are approximately 500 million cases of malaria, causing nearly one million deaths, mostly in Africa. It is estimated that a child under five years old dies every 30 seconds from the disease. Malaria is usually caused by plasmodium. After the bite of infected female anopheles, plasmodium is injected into human body. 10 to 20 days later, typical clinical manifestation shows, which can be classified to 4 phases: stadium frigoris stage, hyperpyrexia Stage, sweating stage and diapauses stage. After repeated paroxysm of malaria, anaemia, hepatomegaly, splenomegaly, even dangerous symptoms such as cerebral, ultrahyperpyrexia, cold syncope and gastrointestinal malaria may occur, which is serious even fatal to life. Due to the climbing of tolerance to the existing drugs, the incidence rate of malaria daily increases, which demand the invention of new type therapeutic anti-malaria drugs.
Plasmodia in erythrocytic stage would hydrolyze host hemoglobin in the acidic food vacuole to obtain necessary energy and amino acids. Biological studies indicate that plasmodia food vacuole possess a series of hydrolytic enzymes, such as plasmepsins, falcipains and falcilysins. These enzymes have become potential targets for malaria chemotherapy.
The molecular weight of falcipain is about 21,000 to 30,000. The highest hydrolytic activity presents at pH 4-6.5 and its active sites contain cysteine residues. Plasmodium's falcipains belongs to the papain-family cysteine proteases. The known plasmodium's falcipain proteins have four subtypes, which are falcipain-1, falcipain-2A, falcipain-2B and falcipan-3. In addition, falcipain 1 is the first plasmodium cysteine protease obtained by exogenous expression. Biological studies have shown that falcipain 1 has no effect on asexual stage of plasmodium, but has significant effects on ovarian function. Falcipain-2A and flacipain-2B have 97% homology and only differ in the seventh amino acid. Through the detection of oligonucleotide probes, the expression level of falcipain-2B mRNA is lower than falcipain-2A. However, in the late vegetative stage of plasmodium, the time-dependence and peak value of expression of falcipain-2A and falcipain-2B are very similar, which indicate that two different subtypes have similar biological function. Falcipain-3 and falcipain-2 have 66.6% homology in the catalytic domain, but express in different stage. The expression of falcipain-2 reaches a peak in the vegetative stage, but falcipain-3's expression peaks at more mature stage. In these subtypes, studies on falcipain-2 are broader and deeper, and therefore, and their inhibitors development are also subjected to more extensive attention.
It has been a long history since the Traditional Chinese Medicine was used to treat malaria. For example, according to the book Suwen about Acupuncture for Malaria, acupuncture was used to prevent malaria. A lot of Chinese herbs, not only Artemisia apiacea, are used as folk medicines against malaria, including Clematis chinensis, Kyllinga brevifolia, Java Brucea, Antipyretic dichroa, Centipeda minima, Areca nut, Potentilla discolor, Ranunculus sceleratus, et al. The compound artemisinine that is found in Artemisia apiacea show good effect in treating malaria. The investigators of this invention built a compound library with more than 2,000 natural compounds by years' hard work. By screening the compounds in the library, the investigators discovered a kind of flavonoid glycoside compounds with anti-malaria effect.